We propose to develop the synthesis of protected peptide fragments on solid supports using amino acid esters of oximes as the anchoring groups. We have found already that peptides can be assembled on oxime-containing polymeric supports under conditions similar to those customarily employed in solid-phase synthesis by the usual Merrifield stepwise approach. By mild treatment with hydrazine, it appears that protected peptide fragments can be removed in their hydrazide form which then can be converted to an azide for further coupling of the fragments. We hope now to establish conditions for removing the protected peptides from the polymers with the C-terminal amino acid in its free carboxyl form. Also, we wish to determine which of the oxime-containing polymers we have prepared is best for the fragment synthesis. The development of the polymer-bound oxime ester method should enable us to synthesize peptides containing up to fifty to sixty amino acids by a combination of fragment synthesis and condensation. Because this approach should aid the preparation of polypeptides which have single amino acid replacements in crucial regions, synthetic studies of structure-activity relationships for a variety of rather large biologically important peptides should be facilitated. Among the polypeptides we plan to prepare are a truncated model of pancreatic trypsin inhibitor (Kunitz) and the neurotoxins apamin and sea anemone toxin II, as well as analogs of the latter toxin. We expect to continue to submit a variety of oxime derivatives to the National Cancer Institute's antitumor screening program.